Exposure to sixty minutes of hyperoxia upregulates myocardial humanins in patients with coronary artery disease - a pilot study.

In experimental setting the concept of myocardial preconditioning by hyperoxia has been introduced and different intracellular protective mechanisms and their effects have been described. To study whether similar protective phenotype can be induced by hyperoxia also in humans, gene expression profile after hyperoxic exposure was analyzed. Adult patients were randomized to be ventilated with either FiO2 0.4 (n = 14) or 1.0 (n = 10) for 60 minutes before coronary artery bypass grafting. A tissue sample from the right atrial appendage was taken for gene analysis and expression profile analysis on genome wide level by RNA-seq analysis was applied. Exposure to > 96% oxygen for 60 minutes significantly changed the expression of 20 different genes, including upregulation of two different humanins - MTRNR2L2 and MTRNR2L8, and activated a "cell survival" network as detected by Ingenuity Pathway Analyses. We concluded that administration of > 96% oxygen for 1 hour changes gene expression in the myocardium of the patients with coronary artery disease and may enhance cell survival capability.

Pre-treatment with hyperoxia before coronary artery bypass grafting - effects on myocardial injury and inflammatory response.

BACKGROUND: In experimental studies, exposure to hyperoxia for a limited time before ischaemia induces a low-grade systemic oxidative stress and evokes an (ischaemic) preconditioning-like effect of the myocardium. We hypothesised that hyperoxia before cardioplegia could protect the myocardium against necrosis and stunning caused by ischaemia-reperfusion. METHODS: Forty patients undergoing coronary artery bypass grafting were randomly exposed to an oxygen fraction of 0.4 or > 0.96 in inspired air on an average of 120 min before cardioplegia. Blood for troponin I, creatine kinase-MB, lactate, glutathione and interleukin-6 was sampled from arterial and coronary sinus cannulae during 20 min of reperfusion. Additional arterial samples were drawn 60 min after declamping and in the first post-operative morning. The cardiac index and right and left ventricular stroke work indices were measured before sternotomy and up to 12 h post-operatively. RESULTS: Troponin I, creatine kinase-MB and lactate did not differ between the groups. Hyperoxic pre-treatment had no impact on the post-operative haemodynamic indices measured with the thermodilution pulmonary artery catheter. More oxidised glutathione was released in the hyperoxia group in the first minute of reperfusion (P = 0.015). Hyperoxic pre-treatment abolished the myocardial release of interleukin-6 during 20 min of reperfusion (P = 0.021 vs. controls). In the first post-operative morning, interleukin-6 was higher in the hyperoxia group [127.0 (86.0-140.0) vs. 85.2 pg/ml (66.6-94.5 pg/ml); P = 0.016]. CONCLUSIONS: Exposure to >96% oxygen before cardioplegia did not attenuate ischaemia-reperfusion injury of the heart in patients undergoing coronary artery bypass grafting. The only potentially beneficial effect observed was the decreased transmyocardial release of interleukin-6.